biostudies-literatureDay JDNIBIB NIH HHSAHRQ HHSNINDS NIH HHSNational Institutes of Health754127https://www.ebi.ac.uk/biostudies/studies/S-EPMC8582279biostudies-literatureUnknown12COVID-19 presentations range from mild to moderate through severe disease but also manifest with persistent illness or viral recrudescence. We hypothesized that the spectrum of COVID-19 disease manifestations was a consequence of SARS-CoV-2-mediated delay in the pathogen-associated molecular pattern (PAMP) response, including dampened type I interferon signaling, thereby shifting the balance of the immune response to be dominated by damage-associated molecular pattern (DAMP) signaling. To test the hypothesis, we constructed a parsimonious mechanistic mathematical model. After calibration of the model for initial viral load and then by varying a few key parameters, we show that the core model generates four distinct viral load, immune response and associated disease trajectories termed "patFrontiers in immunologyDivergent COVID-19 Disease Trajectories Predicted by a DAMP-Centered Immune Network Model.PMC8582279R21 NS113055T32 HS026121U01 EB021960Singh HRanard BLVodovotz YDay JDPark SChow CCfalseDivergent COVID-19 Disease Trajectories Predicted by a DAMP-Centered Immune Network Model.COVID-19 presentations range from mild to moderate through severe disease but also manifest with persistent illness or viral recrudescence. We hypothesized that the spectrum of COVID-19 disease manifestations was a consequence of SARS-CoV-2-mediated delay in the pathogen-associated molecular pattern (PAMP) response, including dampened type I interferon signaling, thereby shifting the balance of the immune response to be dominated by damage-associated molecular pattern (DAMP) signaling. To test the hypothesis, we constructed a parsimonious mechanistic mathematical model. After calibration of the model for initial viral load and then by varying a few key parameters, we show that the core model generates four distinct viral load, immune response and associated disease trajectories termed "pat2021-01-01T00:00:00Z20212025-04-05T10:51:49.152Z2022-02-11T12:50:30.718ZS-EPMC85822793477736610.3389/fimmu.2021.754127